Despite significant advances in surgical procedures, antimicrobial agents, and intravenous fluid therapy, there still exists appreciable morbidity and mortality from surgical sepsis. One proposed factor contributing to the pathogenesis of sepsis is host immunosuppression. Clinical infections may be due in part to impairment in host defense mechanisms due to therapy, surgery or other multi-factoral mechanisms. The efficacy of immunotherapy in sepsis is presently not clearly defined. The purpose of the proposed research is to continue to delineate the role of immunostimulation in the prevention and treatment of surgical sepsis. The chemically-defined, non-specific immunostimulant glucan-P and its water soluble component, glucan-S, will be utilized in a variety of animal models selected to closely simulate clinical situations in man. These include gram-negative peritonitis and various microbial infections following surgery-associated immunodepression. Aspects studied in the various murine models will include bacterial dynamics, alterations in immune parameters, with emphasis on the role of the macrophage, and clinical, biochemical, and histological changes in the host. Special attention in our studies of experimental peritonitis will be given to the interaction of glucan immunostimulation and antibiotic therapy. Studies will be undertaken to ascertain whether antibiotics in combination with glucan immunotherapy will produce a synergistic effect in ameliorating sepsis. A model of chronic abdominal sepsis will also be established to ascertain the ability of glucan immunostimulation to prevent formation of intra-abdominal abscesses and chronic sepsis. The role of post-surgical immunodepression as a cause of sepsis will be studied and attempts made to modify such sepsis by immunostimulation. An analysis of macrophage and T and B lymphocyte function will be made in the various experimental models. The pathophysiology of the septic process and alterations in the host defense mechanisms secondary to glucan therapy will be documented and correlated with clinical outcome. Results of the proposed research are anticipated to lead to new concepts and modalities of therapy for sepsis.